We describe the viral gene expression cascade at the single-cell level, showing bifurcations and bottleneck states. Host gene expression changes are related to viral transcription. The role of cellular signaling pathways in infection is studied using trajectory analysis and the importance of the Nrf2 transcription factor studied in follow-up experiments. Overall design: Human primary fibroblasts were infected with HSV-1 and single-cell RNA-sequencing was performed at different early time points after infection.
Single-cell RNA-sequencing of herpes simplex virus 1-infected cells connects NRF2 activation to an antiviral program.
Subject
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ZFP36L2 is required for self-renewal of early burst-forming unit erythroid progenitors.
Specimen part
View SamplesEarly erythroid progenitors were isolated from mouse E14.5 fetal liver. After cell lysing, control IgG or RBP specific antibody were incubated with cell lysis. Immunoprecipitation followed by microarray experiments were carried out to identify transcripts that are immunoprecipitated by either control IgG or RBP specific antibody.
ZFP36L2 is required for self-renewal of early burst-forming unit erythroid progenitors.
Specimen part
View SamplesTo analyze target genes of human heat shock transcription factor 1 (HSF1), we first generated two independent HeLa clones (RDT1 and RDT2) expressing an actively mutated hHSF1 (hHSF1RDT), which lacks the regulatory domain that masks its activation domain and possesses a glutamic acid at amino acid 395 instead of a leucine in the suppression domain of the trimerization domain (Fujimoto et al., J. Biol. Chem. 280, 34908-34916, 2005). We also generated a HeLa clone expressing chicken HSF1 (HeLa/cHSF1) to compare its profile of gene expression with those of RDT1 and RDT2 cells (Nakai and Morimoto, Mol. Cell. Biol. 13, 1983-1997, 1993). We then carried out DNA microarray analysis using total RNA isolated from HeLa, HeLa/cHSF1, RDT1, and RDT2 cells grown under normal growth conditions.
Heat shock factor 1 ameliorates proteotoxicity in cooperation with the transcription factor NFAT.
Cell line
View SamplesTranscription factor access to regulatory elements is prevented by the nucleosome. Heat shock factor 1 (HSF1) is a winged helix transcription factor that plays roles in control and stressed conditions by gaining access to target elements, but mechanisms of HSF1 access have not been well known in mammalian cells. We show a physical interaction between the wing motif of human HSF1 and replication protein A (RPA), which is involved in DNA metabolism. Depletion of RPA1 abolishes HSF1 access to the promoter of HSP70 in unstressed conditions, and delays its rapid activation in response to heat shock. The HSF1-RPA complex leads preloading of RNA polymerase II and opens chromatin structure by recruiting a histone chaperone FACT. Furthermore, this interaction is required for melanoma cell proliferation. These results provide a mechanistic basis for constitutive HSF1 access to nucleosomal DNA, which is important for both basal and inducible gene expression.
RPA assists HSF1 access to nucleosomal DNA by recruiting histone chaperone FACT.
Specimen part
View SamplesTranscriptome analysis of control and MALAT1 lncRNA-depleted RNA samples from human diploid lung fibroblasts [WI38]
Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB.
Specimen part, Cell line
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MicroRNA-mRNA interactions in a murine model of hyperoxia-induced bronchopulmonary dysplasia.
Specimen part, Disease, Disease stage, Treatment
View SamplesThe goal of the was to evaluate the mRNA expression profile of non-asthmatic and asthmatic airway smooth muscle. Overall design: RNA Seq was performed on nonasthmatic (n=5 individuals) and asthmatic (n=5 individuals) human airway smooth muscle cells.
Arhgef12 drives IL17A-induced airway contractility and airway hyperresponsiveness in mice.
Sex, Age, Specimen part, Disease, Subject
View SamplesTo clarify inflammatory genes whose expression is suppressed at high temperatures, we performed comprehensive analysis of gene expression by using a DNA microarray. Two independent primary cultures of mouse embryo fibroblasts (MEF1 and MEF2) were treated with LPS for 4 hours, or treated with LPS for 4 hours after the pretreatment with heat shock at 42C for 1 hour, and we identified 100 genes that undergo more than a 3-fold increase with LPS treatment. Remarkably, 86 genes (86%) underwent less than a 2-fold increase after combined treatments with heat shock and LPS in MEF1 and MEF2 cells.
Heat shock transcription factor 1 inhibits expression of IL-6 through activating transcription factor 3.
Specimen part
View SamplesVAChT KDHOM mice have a 70% decrease in the vesicular acetylcholine transporter (VAChT) and this leads to a systemic decrease in ACh release and cardiac dysfunction.
An analysis of the myocardial transcriptome in a mouse model of cardiac dysfunction with decreased cholinergic neurotransmission.
Sex, Age, Specimen part
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